Toward Scalable Fabrication of Hierarchical Silica Capsules with Integrated Micro-, Meso-, and Macropores.

Hierarchical porous structures are ubiquitous in biological organisms and inorganic systems. Although such structures have been replicated, designed, and fabricated, they are often inferior to naturally occurring analogues. Apart from the complexity and multiple functionalities developed by the biological systems, the controllable and scalable production of hierarchically porous structures and building blocks remains a technological challenge. Herein, a facile and scalable approach is developed to fabricate hierarchical hollow spheres with integrated micro-, meso-, and macropores ranging from 1 nm to 100 µm (spanning five orders of magnitude). (Macro)molecules, micro-rods (which play a key role for the creation of robust capsules), and emulsion droplets have been successfully employed as multiple length scale templates, allowing the creation of hierarchical porous macrospheres. Thanks to their specific mechanical strength, these hierarchical porous spheres could be incorporated and assembled as higher level building blocks in various novel materials.

The diffusible factor synthase XanB2 is a bifunctional chorismatase that links the shikimate pathway to ubiquinone and xanthomonadins biosynthetic pathways.

The diffusible factor synthase XanB2, originally identified in Xanthomonas campestris pv. campestris (Xcc), is highly conserved across a wide range of bacterial species, but its substrate and catalytic mechanism have not yet been investigated. Here, we show that XanB2 is a unique bifunctional chorismatase that hydrolyses chorismate, the end-product of the shikimate pathway, to produce 3-hydroxybenzoic acid (3-HBA) and 4-HBA. 3-HBA and 4-HBA are respectively associated with the yellow pigment xanthomonadin biosynthesis and antioxidant activity in Xcc. We further demonstrate that XanB2 is a structurally novel enzyme with three putative domains. It catalyses 3-HBA and 4-HBA biosynthesis via a unique mechanism with the C-terminal YjgF-like domain conferring activity for 3-HBA biosynthesis and the N-terminal FGFG motif-containing domain responsible for 4-HBA biosynthesis. Furthermore, we show that Xcc produces coenzyme Q8 (CoQ8) via a new biosynthetic pathway independent of the key chorismate-pyruvate lyase UbiC. XanB2 is the alternative source of 4-HBA for CoQ8 biosynthesis. The similar CoQ8 biosynthetic pathway, xanthomonadin biosynthetic gene cluster and XanB2 homologues are well conserved in the bacterial species within Xanthomonas, Xylella, Xylophilus, Pseudoxanthomonas, Rhodanobacter, Frateuria, Herminiimonas and Variovorax, suggesting that XanB2 may be a conserved metabolic link between the shikimate pathway, ubiquinone and xanthomonadin biosynthetic pathways in diverse bacteria.

Sequential release of autophagy inhibitor and chemotherapeutic drug with polymeric delivery system for oral squamous cell carcinoma therapy.

Autophagy inhibition is emerging as a new paradigm for efficient cancer therapy by overcoming multidrug resistance (MDR). Here, we developed an effective chemotherapeutic system for oral squamous cell carcinoma (OSCC) based on polymeric nanomicelles for codelivery of the anticancer drug doxorubicin (DOX) and the autophagy inhibitor LY294002 (LY). The hydrophobic DOX was conjugated onto a hydrophilic and pH-responsive hyperbranched polyacylhydrazone (HPAH), forming the DOX-conjugated HPAH (HPAH-DOX). Due to its amphiphilicity, HPAH-DOX self-assembled into nanomicelles in an aqueous solution and the autophagy inhibitor LY could be loaded into the HPAH-DOX micelles. The release of DOX and LY from the LY-loaded HPAH-DOX micelles was pH-dependent, whereas LY was released significantly faster than DOX at a mildly acidic condition. The in vitro evaluation demonstrated that the LY-loaded HPAH-DOX micelles could rapidly enter cancer cells and then release LY and DOX in response to an intracellular acidic environment. Compared to the HPAH-DOX micelles and the physical mixture of HPAH-DOX and LY, the LY-loaded HPAH-DOX micelles induced a higher proliferation inhibition of tumor cells, illustrating a synergistic effect of LY and DOX. The preferentially released LY inhibited the autophagy of tumor cells and made them more sensitive to the subsequent liberation of DOX. The polymeric codelivery system for programmable release of the chemotherapy drug and the autophagy inhibitor provides a new platform for combination of traditional chemotherapy and autophagy inhibition.

Low temperature and template-free synthesis of hollow hydroxy zinc phosphate nanospheres and their application in drug delivery.

Hollow hydroxy zinc phosphate nanospheres (HZnPNSs) with sizes of 30-50 nm and wall thicknesses of about 7 nm were synthesized using a template-free method through wet precipitation of Zn(NO3)2·6H2O and (NH4)2HPO4 at temperatures of 0, 10, and 20 °C. The crystal structures, morphologies, sizes and pore properties, Zn/P molar ratios, and thermal stability properties of nanoparticles have been carefully examined. The methyl-thiotetrazole assay measurements proved the low cell cytotoxicity of the material. The protein adsorption of negatively charged bovine serum albumin (BSA) and positively charged lysozyme on HZnPNSs was also investigated. The results showed that HZnPNSs had high protein adsorption affinity. Furthermore, anticancer doxorubicin as a model drug was used to evaluate the entrapment efficiency and drug loading capacity of HZnPNSs, which showed high loading capacity (>16 wt %) for doxorubicin. The confocal laser scanning microscope observations showed that the drug could be efficiently delivered into cells.

NIR-responsive and lectin-binding doxorubicin-loaded nanomedicine from Janus-type dendritic PAMAM amphiphiles.

Janus-type dendritic poly(amido amine) (PAMAM) amphiphiles Dm-Lac-D3DNQ were synthesized by connecting hydrophobic diazonaphthoquinone (DNQ)-decorated PAMAM dendron D3 (generation 3) and hydrophilic lactose (Lac)-decorated PAMAM dendrons Dm (generations 0-2, m = 0-2) via click chemistry. They self-assembled into the DNQ-cored micelles dangled by densely free Lac groups in aqueous solution. Irradiated by 808 nm laser and 365 nm lamp, both NIR- and UV-sensitivity of micelles were characterized by time-resolved UV-vis spectroscopy. The characteristic absorption intensity of DNQ progressively decreased and then leveled off. Moreover, the bigger the micelles, the more the irradiation time for finishing Wolff rearrangement of DNQ. TEM further confirmed that most of the micelles disassembled after 30 min of 808 nm laser irradiation. The Lac-coated micelles showed binding with RCA(120) lectin, as monitored by UV-vis and DLS. The apparent drug-release rate of doxorubicin (DOX) loaded nanomedicine nearly doubled after 10 min of 808 nm laser irradiation, presenting a NIR-triggered drug-release profile. Moreover, the DOX-loaded nanomedicine presented a phototriggered cytotoxicity that was close to free DOX, and they could quickly enter into HeLa cells, as evidenced by MTT assay, flow cytometry, and CLSM. Importantly, this work provides a versatile strategy for the fabrication of NIR-responsive and lectin-binding dendrimer nanomedicine, opening a new avenue for "on-demand" and spatiotemporal drug delivery.

Evaluation of osteoinduction and proliferation on nano-Sr-HAP: a novel orthopedic biomaterial for bone tissue regeneration.

Hydroxyapatite (HAP), a CaP compound similar to the mineral phase present in bone, has excellent biocompatibility but little osseous inductivity. In this study, we evaluated the novel nano-Sr-HAP, in which the calcium of hydroxyapatite was substituted with strontium, which acts as a bone-forming agent. Its biocompatibility and osteoinduction were assayed using marrow mesenchymal stem cells (MSCs) and osteoblasts (OBs) in vitro. We were able to demonstrate that nano-Sr-HAP supported increased OB cell adhesion, proliferation and viability up to 4 days in culture when compared with nano-HAP. MSCs cultured with nano-Sr-HAP showed higher alkaline phosphatase (ALP) activity. More extracellular mineralized nodules were found with nano-Sr-HAP compared to nano-HAP, especially in images of ALP staining. We suggest that nano-Sr-HAP powders possess osteoconductive and osteoinductive properties and have the potential to be used in the repair of bone defects caused by osteoporotic fractures.

Full-Color and Switchable Circularly Polarized Light from a Macroscopic Chiral Dendritic Film through a Solid-State Supramolecular Assembly.

Chiral materials displaying chirality across multiple length scales have attracted increasing interest due to their potential applications in diverse fields. Herein, we report an efficient approach for the construction of macroscopic crystal dendrites with hierarchical chirality based on an in situ solid assembly in a block copolymer film. Chiral fluorescent crystals are formed by enantiopure d-/l-dibenzoyl tartaric acid and pyrenecarboxylic acid in a poly(1,4-butadiene)-b-poly(ethylene oxide) film. The chiro-optical activity of the crystalline dendrites can be greatly amplified in the absorption and scattering regions and goes along with the dimension of dendrites. Notably, the chiral dendrites exhibited strong circularly polarized luminescence emission with a high dissymmetric factor (0.03). The enhancement of the quantum yield of the chiral film was up to 28%, which was 14 times higher that of the corresponding fluorescent molecules. The circularly polarized emission bands of the films can be fine-tuned by contriving the emissive bands of fluorescent molecules. More importantly, the chiral signals are able to be wiped when the fluorescent group photodimerizes under UV irradiation. This work provides an efficient way to develop functional materials through solid self-assembly.

Supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases for drug delivery.

Novel supramolecular copolymer micelles with stimuli-responsive abilities were successfully prepared through the complementary multiple hydrogen bonds of nucleobases and then applied for rapid intracellular release of drugs. First, both adenine-terminated poly(ε-caprolactone) (PCL-A) and uracil-terminated poly(ethylene glycol) (PEG-U) were synthesized. The supramolecular amphiphilic block copolymers (PCL-A:U-PEG) were formed based on multiple hydrogen bonding interactions between PCL-A and PEG-U. The micelles self-assembled from PCL-A:U-PEG were sufficiently stable in water but prone to fast aggregation in acidic condition due to the dynamic and sensitive nature of noncovalent interactions. The low cytotoxicity of supramolecular copolymer micelles was confirmed by MTT assay against NIH/3T3 normal cells. As a hydrophobic anticancer model drug, doxorubicin (DOX) was encapsulated into these supramolecular copolymer micelles. In vitro release studies demonstrated that the release of DOX from micelles was significantly faster at mildly acid pH of 5.0 compared to physiological pH. MTT assay against HeLa cancer cells showed DOX-loaded micelles had high anticancer efficacy. Hence, these supramolecular copolymer micelles based on the complementary multiple hydrogen bonds of nucleobases are very promising candidates for rapid controlled release of drugs.

Oxime linkage: a robust tool for the design of pH-sensitive polymeric drug carriers.

Oxime bonds dispersed in the backbones of the synthetic polymers, while young in the current spectrum of the biomedical application, are rapidly extending into their own niche. In the present work, oxime linkages were confirmed to be a robust tool for the design of pH-sensitive polymeric drug delivery systems. The triblock copolymer (PEG-OPCL-PEG) consisting of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic oxime-tethered polycaprolactone (OPCL) was successfully prepared by aminooxy terminals of OPCL ligating with aldehyde-terminated PEG (PEG-CHO). Owing to its amphiphilic architecture, PEG-OPCL-PEG self-assembled into the micelles in aqueous media, validated by the measurement of critical micelle concentration (CMC). The MTT assay showed that PEG-OPCL-PEG exhibited low cytotoxicity against NIH/3T3 normal cells. Doxorubicin (DOX) as a model drug was encapsulated into the PEG-OPCL-PEG micelles. Drug release study revealed that the DOX release from micelles was significantly accelerated at mildly acid pH of 5.0 compared to physiological pH of 7.4, suggesting the pH-responsive feature of the drug delivery systems with oxime linkages. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living cells. MTT assay against HeLa cancer cells showed DOX-loaded PEG-OPCL-PEG micelles had a high anticancer efficacy. All of these results demonstrate that these polymeric micelles self-assembled from oxime-tethered block copolymers are promising carriers for the pH-triggered intracellular delivery of hydrophobic anticancer drugs.

Silver-hydroxyapatite nanocomposites prepared by three sequential reaction steps in one pot and their bioactivities in vitro.

Hydroxyapatite (HA) combined with antimicrobial agents for biomedical application can effectively avoid the bacteria infection, while HA have the good performance. In this study, we prepared silver-hydroxyapatite (Ag-HA) nanocomposites using a one-pot method consisting of three sequential steps of wet chemical precipitation, ion exchange, and a silver mirror reaction. The HA nanoparticles used as the precursor for Ag ion doping were first synthesised by wet chemical precipitation. Next, Ag+ absorbed on HA surface through ion exchange reaction. Glucose was then added to initiate the silver mirror reaction, which made the Ag+ ions reduce to Ag0 and Ag nanoparticles in situ formed on HA nanoparticles. Subsequently, Ag-HA nanocomposites with different Ag content were prepared. X-ray diffraction, SEM, EDX mapping and TEM imaging confirmed that spherical Ag nanoparticles ~20-40 nm in diameter were adhered to the surface of HA nano-rods (0.4-0.8 µm in length and 15-40 nm in diameter). The Ag content (1.9-15.2 wt%) in the Ag-HA nanocomposites was adjusted by varying the feeding Ag/Ca molar ratio (2.0-20%). The cell viability evaluation in vitro proved that Ag-HA nanocomposites had low cytotoxicity to L929 normal cells. Meanwhile, the antibacterial examinations in vitro demonstrated that Ag-HA nanocomposites had obvious antibacterial effects on Gram-positive bacteria, Gram-negative bacteria, and fungus. The antibacterial results were dose-dependent on the accumulation of silver content. The Ag-HA nanocomposites loaded PMMA resins also demonstrated a potential antibacterial activity against S. mutans. This paper presents a convenient and bio-friendly approach for preparing Ag-HA nanocomposites with adjustable Ag content, which are a promising material for biomedical applications.

Hydroxyapatite-Bovine Serum Albumin-Paclitaxel Nanoparticles for Locoregional Treatment of Osteosarcoma.

Osteosarcoma is the most primary type of bone tumor occurring in the pediatric and adolescent age groups. In order to obtain the most appropriate prognosis, both tumor recurrence inhibition and bone repair promotion are required. In this study, a ternary nanoscale biomaterial/antitumor drug complex including hydroxyapatite (HA), bovine serum albumin (BSA) and paclitaxel (PTX) is prepared for post-surgical cancer treatment of osteosarcoma in situ. The HA-BSA-PTX nanoparticles, about 55 nm in diameter with drug loading efficiency (32.17 wt%), have sustained release properties of PTX and calcium ions (Ca2+ ) and low cytotoxicity to human fetal osteoblastic (hFOB 1.19) cells in vitro. However, for osteosarcoma (143B) cells, the proliferation, migration, and invasion ability are significantly inhibited. The in situ osteosarcoma model studies demonstrate that HA-BSA-PTX nanoparticles have significant anticancer effects and can effectively inhibit tumor metastasis. Meanwhile, the detection of alkaline phosphatase activity, calcium deposition, and reverse transcription-polymerase chain reaction proves that the HA-BSA-PTX nanoparticles can promote the osteogenic differentiation. Therefore, the HA-BSA-PTX nanodrug delivery system combined with sustained drug release, antitumor, and osteogenesis effects is a promising agent for osteosarcoma adjuvant therapy.

Synthesis, characterization, and in vitro evaluation of long-chain hyperbranched poly(ethylene glycol) as drug carrier.

A series of novel long-chain hyperbranched poly(ethylene glycol)s (LHPEGs) with biodegradable connections were designed and synthesized in one pot through proton-transfer polymerization using PEG and commercial glycidyl methacrylate as monomers and potassium hydride as catalyst. The LHPEGs were hydrolyzed at neutral pH resulting in the decrease of molecular weights. In vitro evaluation demonstrated that LHPEGs were biocompatible and displayed negligible hemolytic activity. The efficient cellular uptake of LHPEGs was confirmed by flow cytometry and confocal laser scanning microscopy. Moreover, conjugation of a model hydrophobic anticancer drug methotrexate to LHPEGs inhibited the proliferation of a human cervical carcinoma Hela cell line. MTT assay indicated that the conjugated methotrexate dose required for 50% cellular growth inhibition against Hela cells was 20 µg/mL. By combining the advantages of long-chain hyperbranched structure and PEG, LHPEG provides a promising drug carrier for therapeutic fields.

Control of the optical properties of a star copolymer with a hyperbranched conjugated polymer core and poly(ethylene glycol) arms by self-assembly.

A self-assembly approach to tuning the optical properties of a star copolymer is reported herein. The star copolymer HCP-star-PEG with a hyperbranched conjugated polymer (HCP) core and many linear poly(ethylene glycol) (PEG) arms has been prepared successfully. The HCP core was synthesized by Wittig coupling of N-(n-hexyl)-3,6-diformylcarbazole and 1,3,5-bis[(triphenylphosphonio)methyl]benzene tribromide. Subsequently, the linear PEG arms were grafted onto the HCP core by acylhydrazone connection. It was found that the optical properties of HCP-star-PEG in chloroform solution changed on addition of acid. Both (1)H NMR and UV/Vis spectroscopic investigations confirmed that the variation of the optical properties was related to the complexation of the acid and the imine bond in the acylhydrazone group. HCP-star-PEG self-assembled into core-shell micelles in the mixed solvent of chloroform and acetonitrile, which affected the protonation of the imine bond. Therefore the optical properties of HCP-star-PEG can be readily controlled by self-assembly.

Construction and application of a pH-sensitive nanoreactor via a double-hydrophilic multiarm hyperbranched polymer.

A double-hydrophilic multiarm hyperbranched polymer with a hyperbranched poly(amidoamine) (HPAMAM) core and many poly(ethylene glycol) monomethyl ether (MPEG) arms connected by pH-sensitive acylhydrazone bonds (HPAMAM-g-MPEG) was successfully prepared. Benefiting from the cationic dendritic core and PEGylation shell, the double-hydrophilic multiarm hyperbranched polymer was used as a nanoreactor for CdS quantum dots (CdS QDs) synthesis in aqueous solution. The obtained HPAMAM-g-MPEG and CdS/HPAMAM-g-MPEG nanocomposites were carefully characterized by (1)H NMR, (13)C NMR, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible absorption spectroscopy (UV-vis), fluorescence spectroscopy (FL), dynamic light scattering (DLS), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and electronic dispersive X-ray spectroscopy (EDS) analysis. Both (1)H NMR and fluorescence spectroscopy investigations confirmed that the acylhydrazone linkage between the dendritic core and linear arms was readily broken under acidic condition (pH <5.5). When MPEG arms departed from the HPAMAM core, the fluorescence intensity of CdS/HPAMAM-g-MPEG nanocomposites greatly increased. Such pH-responsive behavior of CdS/HPAMAM-g-MPEG nanocomposites was utilized as an exploration of a novel fluorescence probe in an acidic lysosome exemplified by COS-7 cells.

Controlling the particle size of interpolymer complexes through host-guest interaction for drug delivery.

A new method to adjust the particle size of interpolymer complexes has been developed by introduction of host-guest interaction into the dilute aqueous solution of poly(acrylic acid) (PAA) and poly(ethylene glycol) (PEG). Because of the cooperative hydrogen-bonding interaction, PAA can form the interpolymer complexes with PEG. Putting beta-cyclodextrin (beta-CD) into dilute PAA/PEG aqueous solution, the competition between host-guest and hydrogen-bonding interactions happens. The beta-CD/PAA/PEG ternary systems have been well characterized by ultraviolet-visible absorption spectroscopy (UV-vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), diffusion NMR spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR), and solid-state (13)C NMR spectroscopy. The results indicate that the hydrophobic cavity of beta-CD is threaded by linear polymers so that the hydrophilicity of PAA/PEG interpolymer complexes is improved greatly. Adjusting the amounts of beta-CD, the particle size of the interpolymer complexes can be readily controlled. The low cytotoxicity of various beta-CD/PAA/PEG ternary complexes has been confirmed using the MTT assay in COS-7 cell line. Doxorubicin (DOX), an anticancer drug, has been encapsulated into the beta-CD/PAA/PEG ternary complexes. The DOX-loaded beta-CD/PAA/PEG ternary complexes have been analyzed by confocal laser scanning microscopy (CLSM), flow cytometry analysis, and the MTT assay against human cervical carcinoma cell (Hela). The results indicate that beta-CD/PAA/PEG ternary complexes with controlled particle size could be used as safe and promising drug carriers.

Design and synthesis of cationic drug carriers based on hyperbranched poly(amine-ester)s.

Novel cationic drug carriers based on hyperbranched poly(amine-ester)s were successfully prepared through proton-transfer polymerization. Both vinyl and epoxy groups of commercially available glycidyl methacrylate monomer could be polymerized through oxyanionic initiation of triethanolamine in the presence of potassium hydride catalysis. By changing the molar ratios of triethanolamine/glycidyl methacrylate or potassium hydride/triethanolamine, we obtained a series of hyperbranched poly(amine-ester)s. The generation of highly branched poly(amine-ester)s was confirmed by (13)C DEPT-135 NMR and 2D NMR techniques, and their degrees of branching were found to be 0.47 to 0.68. The structure and properties of hyperbranched poly(amine-ester)s were analyzed by dynamic light scattering, gel permeation chromatography, Fourier transformed infrared, differential scanning calorimeter, and zeta-potential measurements. Methyl tetrazolium (MTT) assay suggested that the cell viability after 48 h incubation with hyperbranched poly(amine-ester) concentrations up to 1 mg/mL remained nearly 100% compared with the untreated cells. The high cellular uptake of these cationic polymers was confirmed by flow cytometry and confocal laser scanning microscopy. Furthermore, conjugation of a model hydrophobic anticancer drug chlorambucil to hyperbranched poly(amine-ester)s inhibited the proliferation of MCF-7 breast cancer cells. MTT assay indicated that the chlorambucil dose required for 50% cellular growth inhibition against MCF-7 cells was 120 microg/mL. All of these results show that hyperbranched poly(amine-ester)s are promising materials for drug delivery.

Synthesis and gene delivery of poly(amido amine)s with different branched architecture.

A general strategy to improve the transfection efficiency as well as lower the cytotoxicity for polycationic vectors has been developed. Through the polycondensation addition of N,N'-methylene bisacrylamide and 1-(2-aminoethyl)piperazine in a water/N,N-dimethylformamide cosolvent, a series of cationic poly(amido amine)s with same repeating units but different branched architecture have been prepared. With the increase in branched architecture, the cationic polymers become more and more compact, accompanied by the enhancement of primary and tertiary amino groups. Therefore, the buffering capacities and DNA condensation capabilities of cationic poly(amido amine)s are strengthened greatly, whereas the correspondent cytotoxicity decreases. Correspondingly, the transfection efficiency is improved by more than three orders of magnitude. The results of this study indicate that the gene delivery can be readily regulated by only changing the branched architecture of polycations.

In situ preparation of magnetic nonviral gene vectors and magnetofection in vitro.

Magnetic nonviral gene vectors were in situ prepared in the presence of ferrous salts and hyperbranched poly(ethylenimine)s (HPEI) with different molecular weights. HPEI, one of the most promising nonviral vectors, was not only utilized as the nanoreactor and stabilizer to prepare magnetic nanoparticles, but also skillfully used as a base supplier to avoid introducing alkali hydroxide or ammonia. Magnetic nonviral gene vectors with various magnetite contents and saturation magnetizations were obtained by changing the weight ratio of HPEI to FeSO(4).7H(2)O and the molecular weight of HPEI. MTT assays suggested that the resulting magnetite/HPEI gene vectors had lower cytotoxicity compared with pure HPEI. The magnetite/HPEI nonviral gene vectors were used for magnetofection. It was found that the luciferase expression level mediated by magnetite/HPEI in COS-7 cells under a magnetic gradient field was approximately 13-fold greater than that of standard HPEI transfection.

Controlling the Optical Properties of Hyperbranched Conjugated Polyazomethines through Terminal-Backbone Interactions.

A simple approach to tune the optical properties of the hyperbranched conjugated polymers by only adjusting the terminal-backbone interactions has been reported in this article. Hyperbranched conjugated polyazomethines have been successfully prepared by the reaction of tetramine and dialdehyde. Not only varying the monomer feed ratio to change the quantity of terminal amino groups, but also adopting protonation or complexion with proper dopants (SnCl(2) and ß-cyclodextrin), can alter the interactions between amino terminals and imine bonds in the backbone. Correspondingly, the optical properties of the resulting hyperbranched polymers are controlled.

Development of a multifunctional gold nanoplatform for combined chemo-photothermal therapy against oral cancer.

Aim: To design and fabricate a multifunctional drug-delivery nanoplatform for oral cancer therapy. Materials & methods: Polyethylene glycol-stabilized, PDPN antibody (PDPN Ab)- and doxorubicin (DOX)-conjugated gold nanoparticles (AuNPs) were prepared and evaluated for their cytotoxicity and antitumor efficacy in both chemotherapy and photothermal therapy. Results: The obtained (PDPN Ab)-AuNP-DOX system presents low toxicity, a high drug loading capacity and cellular uptake efficiency. Both in vitro and in vivo experiments demonstrate that (PDPN Ab)-AuNP-DOX has enhanced antitumor efficacy. Treatment with (PDPN Ab)-AuNP-DOX combined with laser irradiation exhibits superior antitumor effects. Conclusion: This (PDPN Ab)-AuNP-DOX system may be used as a versatile drug-delivery nanoplatform for targeted and combined chemo-photothermal therapy against oral cancer.